Pre-Op Erythropoietin Reduces Transfusion Requirements After TKA, THA

By John Henry Dreyfuss, staff.

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  • The major finding of this review was that use of EPO reduced the need for allogeneic transfusion by approximately 60%.
  • Preoperative administration of erythropoietin (EPO) reduces the requirement for allogeneic blood transfusion following total knee arthroplasty.
  • Preoperative EPO was also found to increase postoperative hemoglobin levels.

Preoperative erythropoietin (EPO; Figure 1) administration was found to reduce requirements for allogeneic blood transfusion and to increase postoperative hemoglobin level following total knee arthroplasty (TKA) and total hip arthroplasty (THA), according to results of a systematic review published recently in Medicine (Baltimore). However, the reviewed studies of cost-effectiveness were inconclusive, the authors noted. “Further studies and guidelines specific to blood management in the perioperative stage of total knee and hip arthroplasty are expected,” they wrote.

Figure 1. Erythropoietin.
(Sources: Wikipedia/Wikimedia Commons/Public Domain.)

As many clinicians already know, allogeneic blood transfusion carries risk of serious complications. Blood loss requiring a blood transfusion (Figure 2) is nearly inevitable in THA or TKA surgery. Hence, researchers have sought strategies to reduce the need for transfusion following these surgeries.

One promising approach has been the administration of preoperative EPO. However, the efficacy, cost-effectiveness, and safety of EPO remain controversial. The Medicine reviewers aimed to determine “the hematopoiesis-promoting effect and potential complications, as well as the cost-effectiveness, of preoperative use of EPO in patients scheduled for total hip or knee arthroplasty.”

Figure 2. DHM image of human red blood cells.
(Sources: Wikimedia Commons/Creative Commons/By Egelberg [Own work].)

Losing a large volume of blood, enough to require blood transfusion is virtually inevitable during or after THA or TKA (Figures 3 and 4). Despite its wide use, however, ABT has been reported to be associated with a risk of transmission of infectious disease, increased cost, an immunosuppressive effect, and transfusion-associated graft-versus-host disease.

Consequently, several strategies have been examined that could reduce the need for ABT, including the use of EPO, preoperative autologous blood donation (PABD), and postoperative cell salvage. PABD eliminates the risk of disease transmission and has shown promising results in some trials, but was reported recently to be associated with a higher probability of perioperative transfusion, without reducing the need for ABT.

Optimal Clinical Usage Guidelines

“The latest guidelines from the National Institute for Health and Care Excellence in the UK suggest that EPO be given when the patient has anemia and meets the criteria for blood transfusion, but declines a blood transfusion because of religious beliefs or other reasons, or the appropriate blood type is not available because of the patient's red cell antibodies,” the reviewers explained.

“Our review finds that patients with a normal hemoglobin level may also benefit from preoperative use of EPO and provides evidence for the use of EPO in non-anemic patients. To clarify the indications and contraindications of EPO, more studies regarding this issue are necessary, especially in patients with normal hemoglobin levels,” they added.

The Analysis

The reviewers searched the MEDLINE, EMBASE, Cochrane, and databases for relevant studies that were published between 2000 and 2015. The authors found 15 RCTs involving 2155 patients that were eligible for inclusion in the meta-analysis. The found that the preoperative use of EPO was associated with reduced requirements for allogeneic blood transfusion (odds ratio = 0.41) and higher hemoglobin concentration following surgery (standardized mean difference = 0.86, P<0.001).

They found that complication rates were generally not reported. Cost-effectiveness was also summarized but was not conclusive.

Subgroup analysis revealed the following:

  • EPO versus no EPO: EPO was associated with a lower proportion of patients who needed ABT (OR=0.30, P<0.001) and with a lower volume of allogeneic blood transfused (P=0.01).
  • EPO plus PABD versus PABD alone: Use of EPO was associated with lower exposure to ABT (OR=0.39, P=0.03), but no decrease in the average volume of allogeneic blood transfused.
  • EPO versus PABD: Injection of EPO caused no significant difference either in the proportion of patients receiving ABT (OR=0.65, P=0.25), or in the average volume of allogeneic blood transfused (P=0.64).
  • EPO versus no EPO, EPO plus PABD versus PABD alone, and EPO versus PABD: Use of EPO was associated with higher hemoglobin level after surgery (P<0.001, P=0.006, P=0.008, respectively) and the overall difference between the 3 subgroups was also significant (P<0.001).

After taking all studies into consideration, EPO reduced exposure to ABT (OR=0.41, P < 0.001), but there was no significant difference in the average volume of allogeneic blood transfused (P=0.10)

With regard to safety, a study included in the review found no significant difference between the occurrence of deep vein thrombosis or pulmonary embolism between patients receiving EPO or PABD.

Figure 3. Cement-free implant sixteen days after surgery. Femoral component is cobalt chromium combined with titanium which induces bone growth into the implant. Ceramic head. Acetabular cup coated with bone growth-inducing material and held temporarily in place with a single screw.
(Sources: Wikipedia/Creative Commons/By KimvdLinde - Own work.)

Cost Data

The reviewers noted that data on cost were inconclusive. However, a number of studies evaluated the economics of EPO. In one study, 80,000 IU of epoetin alfa was used, and the total cost was $978. In this study, the cost of a unit of autologous blood was $391 and the cost of a unit of allogeneic blood was $514. “This implied that the patients would have to receive ≥2 units of blood to equal the cost of epoetin alfa. Upon calculation, the average cost per patient in the EPO and PABD group was $1032 and $345, respectively,” the reviewers explained.

A study conducted in Europe found that the additional cost for the use of EPO was €785 per patient and the cost per avoided transfusion was €7300.

Another study found that the cost of patients receiving EPO was higher than of patients receiving PABD. A study evaluating transfusion-related costs in THA and TKA found the “EPO reduced the need for postoperative transfusions in high-risk patients undergoing THA and TKA; however, it was not found to be cost-effective in our model.” Another study came to a similar conclusion: that the use of EPO could reduce the need for ABT, but that it was not cost-effective.

In contrast, the authors of still another study included in the review conducted a cost minimization analysis and showed that preoperative EPO would be significantly less costly than allogeneic blood transfusion and could save $800 per patient undergoing THA and $392 per undergoing TKA patient.

Figure 4. X-ray of total knee replacement, lateral view.
(Sources: Wikipedia/GNU Free/By Frederic Jacquot.)


The major finding of this review was that use of EPO reduced the need for allogeneic transfusion by approximately 60%, which is promising considering the possible complications of ABT.

“Another important result of our analysis was the increased reticulocyte counts (or percentages) and hemoglobin levels after use of EPO. Hemoglobin levels of patients receiving EPO were higher than those of patients who did not receive EPO. Additionally, the growth pattern of hemoglobin and reticulocytes was noteworthy. Data from the included studies indicated that the count (or percentage) of reticulocytes rose within 7 days after the injection of EPO and reached a plateau after 2 to 4 weekly injections given before surgery,” the reviewers explained.

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